Toll-like receptor (TLR) signaling controls inflammation in macrophages by tailoring programs of inflammatory cytokines. TLR-induced inflammation is constrained by Rab GTPases and PI3Ks that modulate Akt and mTOR signaling, while proinflammatory cytokine production is promoted by transmembrane adaptor complexes and SFKs. These molecules operate in the context of high turnover, highly dynamic membranes of dorsal ruffles and macropinosomes at the macrophage surface, viewed in live cells by lattice light sheet imaging and other imaging modalities. Coordinated assembly of membrane domains and signaling pathways provides exquisite orchestration of inflammation and innate immune responses.